Correcting neuromuscular deficits with gene therapy in Pompe disease. Todd AG, McElroy JA, Grange RW. Ann Neurol 2015;78:222-234.
Submitted by Andrew Tarulli, MD, News Science Editorial Board
Pompe disease is a muscle disorder in which a reduction in acid alpha-glucosidase (GAA) results in lysosomal glycogen accumulation, ultimately leading to neuromuscular dysfunction. The authors of this study injected an adeno-associated virus (AAV)9 vector expressing GAA into mouse tibialis anterior at early, intermediate, and late stages of Pompe disease, and measured expression of acetylcholine receptor subunit genes, muscle force production, and glycogen clearance. They found that injection of the AAV9 vector at all stages reduced glycogen accumulation, but that injection only at early stages resulted in improvements in acetylcholine receptor subunit gene expression and muscle force production.
These results support further exploration of AAV-based gene therapy in the treatment of Pompe disease. Similar to the application of similar techniques to other disorders including spinal muscular atrophy, gene therapy appears to be more effective when administered early in the course of Pompe disease. While biochemical defects were improved at any stage of intervention in this study, there was a critical period after which motor endplates remained persistently denervated and neuromuscular function was irrevocably compromised.
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